This project is designed to characterize the potential for differentiation therapy based on molecular mechanisms of differentiation promoters acting on human colon carcinoma. Preliminary observations in a well-characterized system of colonic carcinoma cell lines with diverse biological properties (Brattain et al., 1984) and results obtained in their response to various differentiation promoters, have led us to the hypothesis that the induction of extracellular matrix (ECM) components is a critical step in the differentiation process. Cellular ECM's individual ECM components and combinations of ECM components will be assessed for their ability to induce differentiation responses. Combinations of differentiation promoters, ECM and individual components will be characterized for their ability to enhance the differentiation of partially responsive or completely unresponsive lines to individual differentiation promoting agents. Differentiation and growth control have been closely linked to the expression of autocrine growth factors. It is not known how ECM or ECM components will affect the expression of these genes, but ECM has been shown specifically to induce the expression of differentiated products such as casein in cultured mammary cells. Expression of mRNA's for a stimulatory autocrine factor (transforming growth factor-a) and an inhibitory autocrine factor (transforming growth factor-B) as a function of ECM induced differentiation will be characterized.